Imatinib and doxorubicin implicated in cardiac toxicities
Two drugs — imatinib and doxorubicin — have been implicated in the development of cardiac toxicities in studies published this month.
Researchers in the US report on 10 patients who developed severe congestive
heart failure, without obvious cause, while receiving imatinib for chronic
myeloid leukaemia. The researchers collected clinical data from the patients,
who presented with heart failure after a mean of 7.2 ± 5.4 months
of therapy.
Myocardial biopsies performed on two of these individuals revealed mitochondrial
abnormalities. These findings were confirmed in studies on mice and on
cultured cardiomyocytes. “Our data … suggest that imatinib
is cardiotoxic and, in humans, can lead to severe left ventricular dysfunction
and heart failure,” say the researchers. They suggest that the
issue needs to be examined to determine the magnitude of risk and that
people receiving imatinib should be followed closely for signs and symptoms
of left ventricular dysfunction. They also warn that drugs currently
in development that target the abl enzyme and other non-receptor tyrosine
kinases might be cardiotoxic (published
online on 23 July 2006 in Nature Medicine).
A study by researchers in the Netherlands that followed 22 patients treated
with moderate or high doses of doxorubicin for bone tumours has found
that 27 per cent had systolic dysfunction and 45 per cent had diastolic
dysfunction at 22 years of follow-up. This is compared with an earlier
follow-up at 14 years when 9 per cent were found to have systolic dysfunction
and 18 per cent diastolic dysfunction.
The results suggest that after treatment with anthracyclines there is
ongoing and progressive deterioration of cardiac function and no end
to this is anticipated, the researchers conclude.
They recommend that anthracycline-treated cancer survivors should be
considered for life-long cardiac surveillance (published
online on 20
July 2006 in Annals of Oncology). |
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